Breast Cancer Preoperative Treatment Approved by FDA

Breast Cancer Preoperative Treatment Approved by FDA

Pertuzumab was approved by FDA as a preoperative treatment regimen for early breast cancer patients.

Pertuzumab, also known by its brand name as Perjeta, was already approved in combination with trastuzumab and docetaxel chemotherapy in HER2 positive metastatic breast cancer patients, who are not treated with any chemotherapy or HER2 therapy before.

According to this approval, Pertuzumab will be used along with Trastuzumab and chemotherapy in early, HER2 positive breast cancer patients before undergoing surgery as HR2 expresses a higher level of this protein which is involved in growth and survival of cancer.

The approval decision was granted under the FDA Accelerated Approval Program, an initiative which allows faster drug approvals in diseases with high level of unmet needs.

Accelerated approvals are granted for drugs, which use surrogate endpoints in initial studies.  Surrogate endpoints are intermediate endpoints, which are indicative of the clinical benefit and are incorporated in studies to save time.

However, drugs approved under this program should be evaluated in confirmatory studies using actual endpoints of clinical benefit. Failure to demonstrate the benefits in these studies, can lead to revocation of the approval status.

The accelerated approval of Pertuzumab was based on the results of Phase II, NEOSPHERE study.

NEOSPHERE (NEOadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation study used pathological complete response (pCR) as a surrogate endpoint and investigated the efficacy of Pertuzumab regimen in neoadjuvant, HER2 positive breast cancer patients.

A total of 417 patients was assigned the following four regimens randomly: Pertuzumab in combination with Trastuzumab and Docetaxel, Trastuzumab and Pocetaxel; Pertuzumab and Trastuzumab; Pertuzumab and Docetaxel.

Patients who received Pertuzumab in combination with Trastuzumab and Docetaxel showed a pCR of 39.3 percent, whereas patients who received only Trastuzumab and Docetaxel regimen showed a pCR of 21.5 percent. Overall, the Pertuzumab regimen demonstrated a significant (17.8 percent more) increase in pCR compared to the non-pertuzumab regimen.

Roche, the company which manufactures Pertuzumab, has also submitted additional supportive data from TRYPHAENA, a Phase II study investigating cardiac safety of Pertuzumab, in its supplementary new drug application (sNDA) to US FDA.

TRYPHAENA (ToleRabilitY of Pertuzumab, Herceptin and AnthracyclinEs in NeoAdjuvant breast cancer) study evaluated a total of 225 patients who have HER2 positive early breast cancer. Patients were randomly given one among the following three treatment regimens: Pertuzumab in combination with Trastuzumab and anthracycline chemotherapy, which is followed by Pertuzumab, Trastuzumab and Docetaxel; anthracycline chemotherapy and follow-up by Pertuzumab, Trastuzumab and Docetaxel; and Pertuzumab in combination with Trastuzumab and chemotherapy regimen, which includes both Docetaxel and Carboplatin. Cardiac safety and pCR were measured.

More than 50percent pCR were observed in each of the three arms and the individual pCR values were 56.2 percent, 54.7 percent and 63.6 percent respectively. There were no unexpected or newer cardiac events that occurred.

Roche is also conducting a large, Phase III studies, APHINITY (Adjuvant Pertuzumab and Herceptin in INitial TherapY) with more than 4500 patients. This study is designed to evaluate the disease-free survival (DFS) achieved by comparing Pertuzumab in combination with Trastuzumab and chemotherapy with Trastuzumab and chemotherapy.

The result of this study is expected to be released in 2016. The present accelerated approval will be converted to full approval upon review of the data from APHINITY.

Written by: Janet Grace Ortigas

Sources:  FDA  Roche  Clinical Trials

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